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31.
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2-Halogeno- and 2-methyl-ethanols inhibit alpha-chymotrypsin in the order of their substituted groups: [1] tri- greater than di- greater than mono-, [2] Br- greater than Cl- greater than CH3- greater than F-. The inhibition by the halogeno-ethanols is mediated differently from that by the methyl-ethanols, ethanol, and urea. 相似文献
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The spliceosome is a dynamic macromolecular machine that assembles on pre-messenger RNA substrates and catalyses the excision of non-coding intervening sequences (introns). Four of the five major components of the spliceosome, U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), contain seven Sm proteins (SmB/B', SmD1, SmD2, SmD3, SmE, SmF and SmG) in common. Following export of the U1, U2, U4 and U5 snRNAs to the cytoplasm, the seven Sm proteins, chaperoned by the survival of motor neurons (SMN) complex, assemble around a single-stranded, U-rich sequence called the Sm site in each small nuclear RNA (snRNA), to form the core domain of the respective snRNP particle. Core domain formation is a prerequisite for re-import into the nucleus, where these snRNPs mature via addition of their particle-specific proteins. Here we present a crystal structure of the U4 snRNP core domain at 3.6?? resolution, detailing how the Sm site heptad (AUUUUUG) binds inside the central hole of the heptameric ring of Sm proteins, interacting one-to-one with SmE-SmG-SmD3-SmB-SmD1-SmD2-SmF. An irregular backbone conformation of the Sm site sequence combined with the asymmetric structure of the heteromeric protein ring allows each base to interact in a distinct manner with four key residues at equivalent positions in the L3 and L5 loops of the Sm fold. A comparison of this structure with the U1 snRNP at 5.5?? resolution reveals snRNA-dependent structural changes outside the Sm fold, which may facilitate the binding of particle-specific proteins that are crucial to biogenesis of spliceosomal snRNPs. 相似文献
35.
Has the Earth's sixth mass extinction already arrived? 总被引:1,自引:0,他引:1
Barnosky AD Matzke N Tomiya S Wogan GO Swartz B Quental TB Marshall C McGuire JL Lindsey EL Maguire KC Mersey B Ferrer EA 《Nature》2011,471(7336):51-57
Palaeontologists characterize mass extinctions as times when the Earth loses more than three-quarters of its species in a geologically short interval, as has happened only five times in the past 540?million years or so. Biologists now suggest that a sixth mass extinction may be under way, given the known species losses over the past few centuries and millennia. Here we review how differences between fossil and modern data and the addition of recently available palaeontological information influence our understanding of the current extinction crisis. Our results confirm that current extinction rates are higher than would be expected from the fossil record, highlighting the need for effective conservation measures. 相似文献
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alpha-alpha- Diphenyl-alpha- propoxyacetic acid-l-methyl-4-piperidyl ester hydrochloride(propiverine) significantly decreased the volume-pressure ratio of the rat urinary bladder and suppressed efferent nervous activity of the bladder branch of the pelvic nerve during vesical extension. 相似文献
37.
K. Sakakibara M. Iwamori T. Uchida Y. Nagai 《Cellular and molecular life sciences : CMLS》1981,37(7):712-714
Summary Localization of galactocerebroside in kidney, liver, and lung of hamster was studied by the immunoperoxidase method using an affinity-purified specific antibody. Epithelial cells of the following anatomical sites were labelled with the antibody: distal tubuli, ascending limbs of Henle's loops, and collecting tubuli in kidney; periportal bile ducts and hepatic parenchyma in liver; bronchioli and alveoli in lung. The existence of galactocerebroside in these 3 organs was also confirmed by chemical analysis.This study was supported in part by grants from the Ministry of Education, Science and Culture of Japan, a Research Grant for Intractable Diseases from the Ministry of Health and Welfare of Japan, and a grant from the Mitsubishi Foundation. 相似文献
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Jin D Liu HX Hirai H Torashima T Nagai T Lopatina O Shnayder NA Yamada K Noda M Seike T Fujita K Takasawa S Yokoyama S Koizumi K Shiraishi Y Tanaka S Hashii M Yoshihara T Higashida K Islam MS Yamada N Hayashi K Noguchi N Kato I Okamoto H Matsushima A Salmina A Munesue T Shimizu N Mochida S Asano M Higashida H 《Nature》2007,446(7131):41-45
CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders. 相似文献
40.
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects 总被引:231,自引:0,他引:231
Yamauchi T Kamon J Ito Y Tsuchida A Yokomizo T Kita S Sugiyama T Miyagishi M Hara K Tsunoda M Murakami K Ohteki T Uchida S Takekawa S Waki H Tsuno NH Shibata Y Terauchi Y Froguel P Tobe K Koyasu S Taira K Kitamura T Shimizu T Nagai R Kadowaki T 《Nature》2003,423(6941):762-769
Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin. 相似文献